This two-set volume LNCS 15756 and 15767 constitutes the refereed proceedings of the 21st International Symposium on Bioinformatics Research and Applications, ISBRA 2025, held in Helsinki, Finland, during August 3-5, 2025.

The 66 full papers were carefully reviewed and selected from 167 submissions. This year's symposium brought together leading researchers, scientists, and industry professionals from around the world to share cutting-edge advancements, foster collaboration, and explore the future of bioinformatics and computational biology.